Influence of cold-storage conditions on renal function of autotransplantedlarge pig kidneys

Background. The consequences of ischemia/reperfusion injury (IRI) on delaye d graft function (DGF) and graft survival for kidney recipients remain a ma tter of debate. Several strategies have been proposed to reduce IRI. We hav e shown that adding the anti-ischemic drug trimetazidine (TMZ) to different preservation solutions had beneficial effects on the function of reperfuse d rat and pig kidneys. Methods. We analyzed the renal parameters of reperfused. autotransplanted l arge pigs following transplantation. The left kidneys were first removed an d cold flushed with Euro-Collins (EC) and University of Wisconsin (UW) solu tions (with or without 10(-6) mol/L TMZ) and were stored for 45 hours at 4 degrees C. The kidney was then autotransplanted, and the contralateral kidn eys were removed. Creatinine clearance, natriuresis, proteinuria. the degre e of interstitial fibrosis, the number of CD4, CD8. and macrophage-positive cells, and the amount of vascular cell adhesion molecule-1 were analyzed o n kidney biopsies taken at 2, 4 to 5, and 10 to 12 weeks after surgery. Results. The functions of the transplanted kidneys were better preserved af ter cold flushing with TMZ-supplemented solutions than with TMZ-free soluti ons. Creatinine clearance was higher, and proteinuria was lower in animals transplanted with kidneys cold flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced int erstitial fibrosis and the numbers of infiltrating CD4- and CD8-positive ce lls. Conclusion. These results indicate that the condition of cold preservation may influence long-term kidney graft functions and suggest that, to a certa in extent, TMZ reduces the degree of interstitial fibrosis.